CD44/CD70 blockade and anti-CD154/LFA-1 treatment synergistically suppress accelerated rejection and prolong cardiac allograft survival in mice.
(2011) In Scandinavian Journal of Immunology 74. p.430-437- Abstract
- Current treatments that are efficient in controlling effector T cells responses to allografts have limited efficacy on the accelerated rejection mediated by memory T cells. Effective targeting of alloreactive memory T cells may therefore be explored to improve therapeutic approaches towards solving this problem. In this study, we investigated the synergistic effect of CD44/CD70 blockade and anti-CD154/LFA-1 treatment on the accelerated rejection mediated by memory T cells. While CD44/CD70 blockade had limited effects on the alloresponses of effector T cells in vivo, it diminished the expansion of both CD4(+) and CD8(+) memory T cells in recipients adoptively transferred with donor-sensitized T cells. In combination with anti-CD154/LFA-1... (More)
- Current treatments that are efficient in controlling effector T cells responses to allografts have limited efficacy on the accelerated rejection mediated by memory T cells. Effective targeting of alloreactive memory T cells may therefore be explored to improve therapeutic approaches towards solving this problem. In this study, we investigated the synergistic effect of CD44/CD70 blockade and anti-CD154/LFA-1 treatment on the accelerated rejection mediated by memory T cells. While CD44/CD70 blockade had limited effects on the alloresponses of effector T cells in vivo, it diminished the expansion of both CD4(+) and CD8(+) memory T cells in recipients adoptively transferred with donor-sensitized T cells. In combination with anti-CD154/LFA-1 treatment, CD44/CD70 blockade significantly prolonged cardiac allograft survival in adoptive transfer recipients. We demonstrated that treatment with the combination of all four antibodies (anti-CD154/LFA-1/CD44/CD70) inhibited accelerated rejection by markedly suppressing the alloresponses of effector and memory T cells and reducing the number of graft-infiltration lymphocytes in adoptive transfer recipients. Meanwhile, CD44/CD70 blockade and anti-CD154/LFA-1 treatment synergically enhanced regulatory T cells (Tregs) by increasing the proportion of splenic Tregs and the expression of IL-10 in these recipients. Our findings contribute to the potential design of therapies for accelerated allograft rejection. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2007726
- author
- Shao, Wei ; Yan, Guoliang ; Lin, Yingying ; Chen, Jibing ; Dai, Helong ; Wang, Feng ; Xi, Yanfeng ; Thorlacius, Henrik LU and Qi, Zhongquan LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scandinavian Journal of Immunology
- volume
- 74
- pages
- 430 - 437
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000296081100002
- pmid:21707692
- scopus:80053489224
- ISSN
- 1365-3083
- DOI
- 10.1111/j.1365-3083.2011.02595.x
- language
- English
- LU publication?
- yes
- id
- 54fd6aec-38a9-4c5a-953e-24d89c3b8a1d (old id 2007726)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21707692?dopt=Abstract
- date added to LUP
- 2016-04-04 09:16:29
- date last changed
- 2022-01-29 17:06:11
@article{54fd6aec-38a9-4c5a-953e-24d89c3b8a1d,
abstract = {{Current treatments that are efficient in controlling effector T cells responses to allografts have limited efficacy on the accelerated rejection mediated by memory T cells. Effective targeting of alloreactive memory T cells may therefore be explored to improve therapeutic approaches towards solving this problem. In this study, we investigated the synergistic effect of CD44/CD70 blockade and anti-CD154/LFA-1 treatment on the accelerated rejection mediated by memory T cells. While CD44/CD70 blockade had limited effects on the alloresponses of effector T cells in vivo, it diminished the expansion of both CD4(+) and CD8(+) memory T cells in recipients adoptively transferred with donor-sensitized T cells. In combination with anti-CD154/LFA-1 treatment, CD44/CD70 blockade significantly prolonged cardiac allograft survival in adoptive transfer recipients. We demonstrated that treatment with the combination of all four antibodies (anti-CD154/LFA-1/CD44/CD70) inhibited accelerated rejection by markedly suppressing the alloresponses of effector and memory T cells and reducing the number of graft-infiltration lymphocytes in adoptive transfer recipients. Meanwhile, CD44/CD70 blockade and anti-CD154/LFA-1 treatment synergically enhanced regulatory T cells (Tregs) by increasing the proportion of splenic Tregs and the expression of IL-10 in these recipients. Our findings contribute to the potential design of therapies for accelerated allograft rejection.}},
author = {{Shao, Wei and Yan, Guoliang and Lin, Yingying and Chen, Jibing and Dai, Helong and Wang, Feng and Xi, Yanfeng and Thorlacius, Henrik and Qi, Zhongquan}},
issn = {{1365-3083}},
language = {{eng}},
pages = {{430--437}},
publisher = {{Wiley-Blackwell}},
series = {{Scandinavian Journal of Immunology}},
title = {{CD44/CD70 blockade and anti-CD154/LFA-1 treatment synergistically suppress accelerated rejection and prolong cardiac allograft survival in mice.}},
url = {{http://dx.doi.org/10.1111/j.1365-3083.2011.02595.x}},
doi = {{10.1111/j.1365-3083.2011.02595.x}},
volume = {{74}},
year = {{2011}},
}